Disability in older adults is a frequent, adverse health outcome associated with aging. Population-based and clinical research indicates that disability in older adults is strongly associated with chronic diseases, both singly and in combination, and modified by a host of factors at the individual level. However, there is increasing evidence to suggest that pathogenic factors beyond chronic diseases may play significant roles in the development or progression of disability, as well as being associated with mortality in older adults. This study proposes to evaluate the role of three potential contributors to the pathogenesis of disability: inflammation, hormones, micronutrient deficiencies, singly, in combination, and in relation to existing diseases, impairments and frailty. We propose to evaluate these questions through analysis of already-collected data in the Women's Health and Aging Study (WHAS) I and its ancillary studies, the WHAS II and a study that collected blood, analyzed many measures and stored plasma and serum. WHAS I and II provide data on the 1/3 most disabled and the 2/3's least disabled older women living in the community, respectively. Older women are substantially more likely than older men to live disabled or dependent, and to require long-term care due to this. This study proposes to answer the following research aims using merged data sets that span the full spectrum of function in older women: a) to establish population norms and rates of change for pathogenic biomediators; b) to determine the degree to which these biomarkers explain disability status; c) to evaluate longitudinally the independent and interactive contributions of pathogenic biomediators to disability, over and above that of disease, and the potential role of frailty as a modifier of these relationships; d) to develop screening nomograms for clinical identification of those at high risk of severe disability and assess potential impact of interventions needed to meaningfully delay such progression; and e) produce a Monograph based on WHAS results that describes evidence for a causal pathway to disability and its risk factors. This proposed research is one of three studies that comprise an Interactive Research Project Grant designed to conduct next-generation analyses of the Women's Health and Aging Studies. These 3 projects will explore a range of biological, social and environmental risk factors for disability in older women. These 3 levels of evaluation are anticipated, singly and together, to provide substantive new understanding of opportunities for effective prevention and treatment of disability in older women.